Dynamic cardiac resynchronization therapy by tracking intrinsic conduction

ABSTRACT

Systems and methods for pacing the heart using resynchronization pacing delays that achieve improvement of cardiac function are described. An early activation pacing interval is calculated based on an optimal AV delay and an atrial to early ventricular activation interval between an atrial event and early activation of a ventricular depolarization. The early activation pacing interval for the ventricle is calculated by subtracting the measured AV EA  from the calculated optimal AV delay. The early activation pacing interval is initiated responsive to sensing early activation of the ventricle and pacing is delivered relative to expiration of the early activation pacing interval.

RELATED APPLICATIONS

This application is a divisional application of U.S. patent applicationSer. No. 12/570,167 filed on Sep. 30, 2009, which claims priority fromU.S. Provisional Patent Application Ser. No. 61/195,275, filed on Oct.6, 2008, the entire contents of which are hereby incorporated byreference.

FIELD OF THE INVENTION

The present invention relates generally to cardiac pacing therapy, andmore specifically, to methods and systems for dynamically determiningtiming for the delivery of pacing pulses to achieve cardiacresynchronization.

BACKGROUND OF THE INVENTION

The healthy heart produces regular, synchronized contractions. Rhythmiccontractions of the heart are normally initiated by the sinoatrial (SA)node, which is a group of specialized cells located in the upper rightatrium. The SA node is the normal pacemaker of the heart, typicallyinitiating 60-100 heartbeats per minute. When the SA node is pacing theheart normally, the heart is said to be in normal sinus rhythm.

Cardiac arrhythmia occurs when the heart rhythm is irregular or if theheart rate is too slow or too fast. During an arrhythmic episode, theheart's pumping action may become impaired and blood flow to peripheraltissues may be inadequate. Cardiac arrhythmias have a number ofetiological sources, including tissue damage due to myocardialinfarction, infection, or degradation of the heart's ability to generateor synchronize the electrical impulses that coordinate contractions.Bradyarrhythmia occurs when the heart rhythm is too slow. This conditionmay be caused, for example, by impaired function of the SA node, denotedsick sinus syndrome, or by delayed propagation or blockage of theelectrical impulse between the atria and ventricles. Bradyarrhythmiaproduces a heart rate that is too slow to maintain adequate circulation.Tachyarrhythmia occurs when the heart rate is too rapid. Tachyarrhythmiamay have its origin in either the atria or the ventricles.Tachyarrhythmia occurring in the atria of the heart, for example,includes atrial fibrillation and atrial flutter. Both conditions arecharacterized by rapid contractions of the atria. In addition to beinghemodynamically inefficient, the rapid contractions of the atria mayalso adversely affect the ventricular rate.

Ventricular tachyarrhythmia occurs when electrical activity arises inthe ventricular myocardium at a rate more rapid than the normal sinusrhythm. Ventricular tachyarrhythmia may quickly degenerate intoventricular fibrillation. Ventricular fibrillation is a conditiondenoted by extremely rapid, uncoordinated electrical activity within theventricular tissue. The rapid and erratic excitation of the ventriculartissue prevents synchronized contractions and impairs the heart'sability to effectively pump blood to the body, which is a fatalcondition unless the heart is returned to sinus rhythm within a fewminutes.

Implantable cardiac rhythm management (CRM) systems have been used as aneffective treatment for patients with serious arrhythmias. CRM systemoperate by delivering relatively high energy electrical shocks to theheart to terminate tachyarrhythmia and/or by delivering relatively lowenergy electrical pulses to one or more heart chambers, causing theheart chambers to contract at heart rate that is hemodynamicallysufficient.

Pacing therapy has also been used to improve cardiac output for patientswho suffer from heart failure. Heart failure is frequently related tointraventricular and/or intraventricular conduction defects, e.g.,bundle branch blocks which lead to cardiac dyssynchrony and reducedpumping action. To treat heart failure, CRM systems deliver timed pacingpulses that produce more coordinated contractions of the atria and/orventricles. The pacing pulses are delivered to the heart chambers atspecific intervals to achieve optimal improvement in pumping efficiencyand cardiac output. Cardiac resynchronization pacing may include pacingboth ventricles after a specified atrioventricular delay. Theventricular paces may be delivered simultaneously or separated by aprogrammable offset.

Appropriate specification of various resynchronization pacing delays isneeded to achieve optimal improvement of cardiac function. For thereasons stated above, and for other reasons stated below which willbecome apparent to those skilled in the art upon reading the presentspecification, there is a need in the art for methods and systems thatprovide for determination of timing intervals for cardiacresynchronization therapy. The present invention fulfills these andother needs and provides other enhancements over the prior art.

SUMMARY OF THE INVENTION

Embodiments of the present invention are directed to systems and methodsfor pacing the heart using resynchronization pacing delays that achieveimprovement of cardiac function. One embodiment of the invention isinvolves a method for operating a cardiac pacing device. An earlyactivation pacing interval is initialized by calculating an optimal AVdelay based on intrinsic atrioventricular intervals between an atrialevent and a ventricular depolarization for at least one ventricle anddetermining an atrial to early ventricular activation interval (AV_(EA))between an atrial event and early activation of a ventriculardepolarization for the ventricle. The early activation pacing intervalfor the ventricle is calculated by subtracting the AV_(EA) from thecalculated optimal AV delay. The early activation is started responsiveto sensing early activation of the ventricle. The ventricle is pacedrelative to expiration of the early activation pacing interval.

In some implementations, the AV_(EA) is determined based on an intervalbetween an atrial event and a start of a ventricular depolarization, Q*.In some implementations the AV_(EA) is determined based on the intervalbetween an atrial event and a His Bundle depolarization.

The early activation pacing interval may be initiated responsive tosensing early activation of the right or left ventricle. The ventriclepaced relative to the expiration of the early activation pacing intervalmay be the right ventricle, the left ventricle, or both right and leftventricles. If right and left ventricles are paced, the ventricularpaces may be delivered to both ventricles simultaneously. Alternatively,the right and left ventricular paces may be separated by aninterventricular delay.

An embodiment of the invention is directed to a cardiac rhythmmanagement device that includes electrodes electrically coupled tomultiple chambers of a heart and an implantable pulse generatorconfigured to sense cardiac electrical signals and to deliver pacingpulses via the electrodes. Measurement circuitry coupled to the sensecircuitry is configured to measure one or more cardiac intervals. Theintervals include atrioventricular intervals (AVIs) between an atrialevent and a ventricular depolarization for at least one ventricle and anatrial event to early ventricular activation interval (AV_(EA)) betweenan atrial event and early activation of a ventricular depolarization forthe ventricle. Optimization circuitry calculates an optimal AV delaybased on the measured atrioventricular intervals and calculates an earlyactivation pacing interval for the ventricle by subtracting the measuredAV_(EA) from the calculated optimal AVD. A pacing interval controllerstarts the early activation in response to sensing early activation ofthe ventricle. Pacing therapy circuitry delivers pacing pulses to theventricle relative to expiration of the early activation pacinginterval.

For example, in one implementation, the atrial to early ventricularactivation interval comprises an interval between the atrial event and astart of a ventricular depolarization, Q*. In one embodiment, the atrialto early ventricular activation interval comprises an interval betweenthe atrial event and the His Bundle depolarization.

Yet another embodiment of the invention is directed to a method ofoperating a cardiac pacing device. An atrial (A-A) interval and anintrinsic atrioventricular interval (AVI) of a first cardiac cycle aremeasured. A pacing escape interval for a synchronized ventricularchamber is calculated based on the measured A-A interval and themeasured AVI. The pacing escape interval is started responsive tosensing an intrinsic ventricular rate chamber depolarization of thefirst cardiac cycle. During a second cardiac cycle immediately followingthe first cardiac cycle, a ventricular synchronized chamber is pacedrelative to expiration of the pacing escape interval. For eachsubsequent cardiac cycle, the pacing escape interval is recalculatingbased at least on a measured A-A interval from an immediately previouscardiac cycle.

According to some implementations, the rate chamber is the rightventricle and the synchronized chamber is the left ventricle.Alternatively, the rate chamber may be the left ventricle and thesynchronized chamber may be the right ventricle.

In one implementation, the pacing escape interval is based on adifference between the intrinsic atrioventricular interval of the firstcardiac cycle and an optimized synchronized chamber atrioventriculardelay. In one implementation, the pacing escape interval comprises adifference between an intrinsic atrioventricular interval of the firstcardiac cycle and an optimized synchronized chamber atrioventriculardelay subtracted from the A-A interval of the first cardiac cycle.

Another embodiment of the invention involves a cardiac rhythm managementdevice. Measurement circuitry of the cardiac rhythm management devicemeasures intervals between atrial events and atrioventricular intervals(AVIs) between an atrial event and a ventricular depolarization.Optimization circuitry calculates a pacing escape interval for asynchronized ventricular chamber based on a measured A-A interval and ameasured AVI for a first cardiac cycle. A pacing interval controllerstarts the pacing escape interval in response to sensing an intrinsicventricular rate chamber depolarization of the first cardiac cycle.Pacing therapy circuitry delivers pacing to a ventricular synchronizedchamber relative to expiration of the pacing escape interval during asecond cardiac cycle immediately following the first cardiac cycle. Theoptimization circuitry is configured to recalculate the pacing escapeinterval for each subsequent cardiac cycle based at least on a measuredA-A interval from an immediately previous cardiac cycle.

For example, in some implementations, the pacing escape interval may bebased on a difference between the intrinsic atrioventricular interval ofthe first cardiac cycle and an optimized synchronized chamberatrioventricular delay. In some implementations, the pacing escapeinterval comprises a difference between an intrinsic atrioventricularinterval of the first cardiac cycle and an optimized synchronizedchamber atrioventricular delay subtracted from the A-A interval of thefirst cardiac cycle.

The above summary of the present invention is not intended to describeeach embodiment or every implementation of the present invention.Advantages and attainments, together with a more complete understandingof the invention, will become apparent and appreciated by referring tothe following detailed description and claims taken in conjunction withthe accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a timing diagram that illustrates suboptimal pacing thatarises from the use of static pacing delays;

FIG. 2 is a timing diagram having cardiac cycles wherein ventricularpacing is triggered by early activation of the ventriculardepolarization in accordance with embodiments of the invention;

FIG. 3 is a flow diagram that illustrates a process for pacing based onearly ventricular activation in accordance with embodiments of theinvention;

FIG. 4 is a timing diagram that illustrates pacing the synchronizedventricular chamber in accordance with embodiments of the invention;

FIG. 5 is a flow diagram illustrating a process of pacing using anoptimized pacing delay for an LV pace that is initiated by an intrinsicRV depolarization occurring in an immediately preceding cardiac cycle inaccordance with embodiments of the invention;

FIG. 6A shows an embodiment of a therapy device that may be used todeliver pacing therapy in accordance with embodiments of the invention;

FIG. 6B illustrates an embodiment of a therapy device for deliveringpacing therapy including a His lead having a His electrode arranged tosense His bundle depolarizations in accordance with embodiments of theinvention; and

FIG. 7 is a block diagram depicting various components of a system thatmay be used to deliver pacing therapy in accordance with embodiments ofthe invention.

While the invention is amenable to various modifications and alternativeforms, specifics thereof have been shown by way of example in thedrawings and will be described in detail below. It is to be understood,however, that the intention is not to limit the invention to theparticular embodiments described. On the contrary, the invention isintended to cover all modifications, equivalents, and alternativesfalling within the scope of the invention as defined by the appendedclaims.

DETAILED DESCRIPTION OF VARIOUS EMBODIMENTS

In the following description of the illustrated embodiments, referencesare made to the accompanying drawings, which form a part hereof, and inwhich is shown by way of illustration, various embodiments in which theinvention may be practiced. It is to be understood that otherembodiments may be utilized, and structural and functional changes maybe made without departing from the scope of the present invention.

Systems, devices or methods according to the present invention mayinclude one or more of the features, structures, methods, orcombinations thereof described herein below. For example, a device orsystem may be implemented to include one or more of the advantageousfeatures and/or processes described below. It is intended that suchdevice or system need not include all of the features described herein,but may be implemented to include selected features that provide foruseful structures and/or functionality. Such a device or system may beimplemented to provide a variety of therapeutic or diagnostic functions.

Mechanical contractions in the heart are triggered by waves ofelectrical depolarization that travel through the cardiac tissue. In ahealthy heart, a depolarization wave for each cardiac cycle is initiatedat the sinoatrial node and travels through the AV node, the His bundle,the left and right bundle branches and the Purkinje fibers to causecontractions of the ventricles. Due to age, disease, damage frommyocardial infarction, and/or other degradation, the pathways and/ortissues involved in conduction of the depolarization wavefront maybecome compromised.

Pacemakers deliver electrical pacing pulses to the heart to producecontractions of the heart chambers in synchrony and at a rate sufficientto meet the patient's metabolic demand. Pacing therapy involves theimplementation of timing intervals between various events during acardiac cycle. The timing intervals may be used to control the rate ofheart chamber contractions and/or the synchrony between heart chambercontractions. For example, for patients whose intrinsic heart rate istoo slow, pacing assists the heart in contracting at a rate that issufficient to provide blood flow to meet the patient's metabolicrequirements. For patients suffering from heart failure (HF), cardiacpacing may be used to ensure that the contractions of the heart chambersoccur in a timed sequence that improves heart function.

Pacemakers typically include intracardiac electrodes arranged to be inelectrical contact with the myocardium and configured to sense cardiacdepolarization signals and/or deliver cardiac pacing pulses in a timedsequence during cardiac cycles. For example, during a cardiac cycle,pacing escape intervals (pacing delays) may be established between aright or left atrial event and a right or left ventricular pace (AVD)and/or between a ventricular event in one chamber and a ventricularevent in the opposite chamber (IVD). In applications having bi-atrialsensing and/or pacing capability, a pacing delay may be establishedbetween an atrial event in one chamber and an atrial event in theopposite chamber (IAD). One or more of the pacing delays may be adjustedto a predetermined value to enhance the pumping action of the heart. Forexample, in cardiac resynchronization pacing, the setting of the AVDand/or the IVD and/or the IAD can have a significant impact onhemodynamic function. These pacing escape intervals may be set topromote fusion between the left and right chamber depolarizations and/orto enhance ventricular preload.

Determining optimal pacing intervals, such as the AVD and/or IVD, mayinvolve measurement of intrinsic conduction data while the patient is atrest or at a specified cardiac rate. One technique for determiningoptimal pacing escape intervals is described in commonly owned U.S. Pat.No. 7,123,960, which is incorporated herein by reference in itsentirety.

Over time, previously computed optimal pacing delays may becomesuboptimal due to changing patient conditions including diseaseprocesses, myocardial infarction, and/or other factors which alter thecardiac response. Even if re-optimization is performed, pacing may occurusing suboptimal pacing delays during periods between there-optimization processes Embodiments of the invention are directed toapproaches to maintain optimal cardiac resynchronization pacing on abeat-by-beat basis.

Embodiments of the invention are directed to starting pacing delays forone or multiple sites in the RV, one or multiple sites in the LV, orboth the RV and the LV, wherein the pacing delays are triggered by earlyintrinsic activation conducted to the ventricle from the AV node. Earlyactivation may be detected by a variety of approaches, includingdetecting an initial deflection of the QRS complex, denoted Q*, and/orby detecting an indication of the early activation in a signal sensed ata location proximate to the His bundle.

A number of HF patients have intact AV conduction with LBBB whichresults in ventricular dyssynchrony due to significantly delayed leftventricular contractions. Cardiac function for these patients can beimproved by consistent pacing at one or multiple ventricular sites toachieve fusion between the left ventricular (LV) paced wavefront and theintrinsic conduction from the AV node. In some HF patients, it isadvantageous to provide consistent RV pacing at one RV site or multipleRV sites triggered by early activation of the RV. The pacing delay(s)for the pacing site(s) may be timed to fuse depolarization wavefrontsfrom multiple RV sites with an intrinsic depolarization. Pacing toachieve fusion of multiple wavefronts produces a more powerful and/ormore coordinated cardiac contraction.

Some embodiments of the invention are directed to LV and/or RV pacingwith pacing delays timed relative to an early activation signal, e.g.,through detection of Q* in the QRS or His bundle sensing. Someembodiments of the invention are directed to triggered LV pacing usingpacing delays based on the timing of a previous intrinsic depolarizationof the RV. The approaches described herein provide for beat-by-beatadjustment of LV and/or RV pacing delays to avoid periods of suboptimalpacing which results from using static pacing delays or pacing delaysthat are optimized periodically.

FIG. 1 illustrates suboptimal pacing that arises from the use of astatic pacing delay, e.g., static AVD_(Opt). FIG. 1 illustrates anatrial sensing/pacing channel 101, a ventricular sensing channel 102,and a ventricular pacing channel 103. The three cardiac cyclesillustrated, cycle 1, cycle 2, cycle 3, each begin with an intrinsic orpaced atrial event A₁, A₂, A₃. For each pacing cycle, an AV pacingdelay, AVD_(Opt), is initiated responsive to atrial events A₁, A₂, A₃.Pacing pulses V_(p1), V_(p2), V_(p3) are delivered to one or bothventricles relative to the expiration of the AVD_(Opt) for each cycle.The pacing pulses V_(p1), V_(p2), V_(p3) may be delivered to oneventricle, or may be biventricular. If biventricular pacing isdelivered, the right and left ventricular paces may be simultaneous orseparated by an interventricular delay.

FIG. 1 illustrates the situation wherein AVD_(Opt) becomes suboptimalover time. In some embodiments, AVD_(Opt) is set to be short enough sothat one or both ventricles are consistently paced. To achieve fusionpacing during a cardiac cycle, the ventricular pacing pulse must bedelivered at a specific instant in time from early activation of theventricular depolarization. Cycle 1 represents a cardiac cycle thatoccurs just after optimization. During Cycle 1, the value of AVD_(Opt)produces a time interval, t₁, between the early activation signalV_(EA1) and the ventricular pace V_(p1) that allows for fusion to occurbetween an intrinsic depolarization and the depolarization evoked by theventricular pace. Over time, the relative timing of AVD_(Opt) and V_(EA)may shift, causing the interval between V_(EA) and the ventricular pacefor the cycle to become longer or shorter. As illustrated in FIG. 1,shifts in V_(EA2) and V_(EA3) causes t₂ and t₃ to become longer than t₁.Changes in the time interval between the early activations V_(EA2),V_(EA3) and the ventricular paces V_(p2), V_(p3) in cycles 2 and 3 canbecome so great that fusion pacing is precluded. In cycles 2 and 3,pacing is suboptimal because time intervals t₂ and t₃ are too long toproduce fusion.

Embodiments of the invention are directed to methods and systemsconfigured to maintain a substantially constant time interval betweensensed early activation and the delivery of the pacing pulse. Thesubstantially constant time interval between the early activation andpacing is optimized to promote fusion between an intrinsic and paceddepolarization wavefronts. FIG. 2 depicts a timing diagram illustratingcardiac cycles wherein ventricular pacing is triggered by earlyactivation of the ventricular depolarization. The early activation ofthe ventricle may be detected by sensing Q* and/or by sensing anactivation at the His bundle, for example. FIG. 2 shows ventricularpacing for three cardiac cycles, cycle 1, cycle 2, cycle 3, beginningwith an intrinsic or paced atrial event A₁, A₂, A₃. The ventricularpacing pulses V_(p1), V_(p2), V_(p3) are delivered independently of theatrial events A₁, A₂, A₃ and are triggered in response to sensingventricular early activation V_(EA1), V_(EA2), V_(EA3). The triggeredventricular pacing results in a substantially constant interval 200between the early activation V_(EA1), V_(EA2), V_(EA3) and theventricular pace V_(p1), V_(p2), V_(p3) beat by beat for each cardiaccycle.

The interval V_(EA)→V_(p) 200 used for the cardiac cycles can beadjusted to a value that promotes consistent fusion pacing. Aspreviously described, in some embodiments, detection of earlyactivation, V_(EA), occurs when an initial deflection of the ventriculardepolarization Q* is sensed. In these embodiments, the V_(EA)→V_(p) 200interval is the time interval between Q* and the ventricular pace. Inother embodiments, V_(EA)→V_(p) 200 interval is the time intervalbetween a sensed activation at the His Bundle and the ventricular pace.In either approach, the optimal V_(EA)→V_(p) interval may be determinedbased on intrinsic conduction delays. In one example, the optimalV_(EA)→V_(p) interval is described by the following equation:V _(EA) →V _(p) =AVD _(Opt) −AV _(EA)

where AVD_(Opt) is a fixed optimal AV delay and AV_(EA) is an intervalbetween an intrinsic or paced atrial event, A, and the early ventricularactivation, V_(EA).

The AVD_(Opt) and AV_(EA) used for computing the pacing intervalV_(EA)→V_(p) may be determined in an initialization phase. Ifbiventricular pacing use used, the V_(EA)→V_(p) interval may bedifferent for LV and RV pacing, e.g., there may be a V_(EA)→V_(p1), forleft ventricular pacing and V_(EA)→V_(pR) for right ventricular pacing,where V_(EA)→V_(pL)≠V_(EA)→V_(pR). As a safety feature, if there is nointrinsic activity sensed up to a predetermined AV delay, then a backuppace to the RV, the LV or both ventricles can be delivered.Additionally, there may be a minimum interval from atrial event to theventricular pace that is allowed to reduce the symptoms of pacemakersyndrome.

FIG. 3 is a flow diagram that exemplifies a process for pacing based onearly ventricular activation. The process includes computingV_(EA)→V_(p) based on the measured conduction delay (AV_(EA)) betweenthe atrial event, A, and the early ventricular activation, V_(EA), andAVD_(Opt). In some embodiments, AVD_(Opt) is calculated as a fraction ofa measured intrinsic AV interval (AVI), e.g., the right ventricular AVI,denoted AVI_(R). In some embodiments, the AVD_(Opt) is calculated as alinear combination of the right AVI (AVI_(R)) and the intrinsic left AVI(AVI_(L)).

During the initialization phase 305, various conduction intervals aremeasured 310, e.g., AV_(EA), QRS width, AVI_(L), AVI_(R). AVD_(Opt) isdetermined 320 based on one or more of the measured conduction intervalsand/or empirically measured coefficients. The measured conduction delaysfor the AV_(EA) interval and/or the conduction intervals used incalculation of AVD_(Opt) may be determined using a single measurement ofa conduction interval or may be determined using a combination ofmultiple measured intervals. The early activation pacing delayV_(EA)→V_(p) is calculated 330 based on the AV_(EA) and AVD_(Opt).

Pacing is delivered 335 using the V_(EA)→V_(p) delay interval. Earlyactivation of the ventricle may be determined based on an initialdeflection of the QRS complex, or activation sensed at the His bundle,for example.

Q* detection may be based on comparison of the ventricular electrogramto a preestablished template. In one method, a Q* template isestablished by averaging a number of initial electrogram waveforms. Q*is then established form the average waveform. Averaging the initialelectrogram waveforms can be performed by aligning a number, M, of QRScomplexes having similar morphology at the peak of the R-wave. Forexample, M may be a number between about 20 and about 50. The QRScomplexes selected for averaging may be identified by the device or byvisual inspection. Various methods of determining Q* from the averagedwaveform may be implemented.

For example, the absolute derivative of the average waveform may becalculated and the results normalized by the maximum derivative. Analgorithm in accordance with one embodiment would then mark the locationof the R-wave of the average waveform by searching for a largest peak.

Another method of identifying Q* involves searching for a flat segmentof the normalized derivative prior to the R-wave. The search may beperformed by calculating the mean and standard deviation (STD) of datapoints within a fixed-length window that moves away from the location ofR-wave to the left (i.e. earlier than R-wave). The data related to theflattest segment of the normalized derivative has the minimum standarddeviation over all the data within the window. The window length can beprogrammed to values between about 20 to about 100 ms. The algorithm maythen set a threshold as the mean+STD of the flat segment. The algorithmwould then start from the flat segment, examine each data point in thenormalized derivative and compare it with the threshold. The Q* point isestablished as the first point after which there are no more than Mconsecutive data points whose values fall below the threshold.Typically, M is set to be a number that spans about 2 ms to about 5 msin time. In one embodiment, the M value has been set to be equivalent to4 ms. The location of Q* is then identified in the original averagedwaveform.

The Q* template is established as a segment of data from the originalaveraged waveform extending for a time T₁ prior to the Q* point and atime T₂ following the Q* point. T₁ and T₂ can be programmed to fall in arange of about 10 to about 100 ms.

After establishment of the template, subsequent cardiac signals arecompared to the template. The search for a Q* point may begin about 200ms after the R-wave of the previous beat (intrinsic) or 300 ms after thepacing pulse of the previous (stimulated) beat. Each incoming data pointin the electrogram and all the past data points within a window(length=T₁+T₂) are cross-correlated with the template to identify Q*.Additional details regarding Q* detection are described in commonlyowned U.S. Pat. No. 6,768,923 which is incorporated herein by reference.

Activation of the His bundle may be implemented by sensing for the Hisdepolarization during a His signal sensing window following the atrialevent in each cardiac cycle. The onset and/or duration of the His signalsensing window may be programmable. In one embodiment, His bundleactivation is indicated by detecting a peak of the His signal.

Upon sensing 340 early activation of the ventricle, the early activationpacing interval V_(EA)→V_(p) is initiated 350. Ventricular pacing to oneor both ventricles is delivered 360 relative to expiration of theV_(EA)→V_(p).

AVD_(Opt) may be calculated during the initialization phase based on themeasured conduction delay between an atrial event, A, and the rightventricular activation (AVI_(R)) and/or the conduction delay between anatrial event and the left ventricular activation, (AVI_(S)), and/orother conduction delays, e.g., the conduction delay between right andleft ventricular activations.

In some embodiments, AVD_(Opt) for a particular patient may be estimatedas a fraction of the AVI_(R), where the fraction used is based on thewidth of the patient's intrinsic QRS waveform. Using this technique,AVD_(Opt), may be calculated as follows:

AVD_(Opt=N) ₁AVI+K_(narrow),for patients having a narrow QRS complex;and

AVD_(Opt=N) ₂AVI+K_(wide), for patient having a wide QRS complex,

where 0<N₁,N₂<1 and N₂≦N₁, and K_(narrow) and K_(wide) may beempirically determined constants.

Values for N₁ may be in a range of about 0.6 to about 0.8, and valuesfor N₂ may be in a range of about 0.4 to about 0.6, for example. Anarrow QRS complex is one having a width of less than about 150 ms, anda wide QRS complex is on have a width greater than 150 ms.

In some embodiments, AVD_(Opt) for a particular patient may be estimatedfrom approximated conduction delays in terms of specified coefficientsK_(T), as:AVD _(Opt) =K ₁ AV _(L) +K ₂ AV _(R) +K ₃

Derivation of the specified coefficients, K_(n) or N_(n) for laterprogramming into the system or for use by a clinician, involvesobtaining clinical population data related to particular values of themeasured conduction parameters to an optimum value of the pacingparameter as determined by concurrent measurement of another parameterreflective of cardiac function (e.g., maximum dP/dt). A linearregression analysis may be performed to derive values of the specifiedcoefficients used in the formula for setting the pacing parameter, thespecified coefficients thus being regression coefficients.

As previously discussed, the techniques for determining AVD_(Opt) and/orAV_(EA) as described herein, may be implemented in a number of differentways. In one implementation, a system for determining the V_(EA)→V_(p)pacing interval includes an external programmer. In an exampleembodiment, one or more intrinsic conduction parameters, as measuredfrom electrogram signals generated by the sensing channels of animplantable cardiac resynchronization device during intrinsic beats, aretransmitted to the external programmer via a wireless telemetry link.The measured conduction data, such as the atrial event to V_(EA)interval, AV_(R), AV_(L), and/or QRS width, may represent averages ofvalues obtained during a specified number of beats. The externalprogrammer then computes the optimal V_(EA)→V_(p) based on a computedAVD_(Opt) and measured AV_(EA). In an automated system, the externalprogrammer then automatically programs the implantable device with thecomputed V_(EA) V_(p) interval, while in a semi-automated system theexternal programmer presents the computed V_(EA) V_(p) interval to aclinician in the form of a recommendation.

In another automated application, an automated system may also be madeup of the implantable device alone which collects conduction data,measures AV_(EA), computes the AVD_(Opt), and then computes the V_(EA)V_(p) accordingly.

In another embodiment, which may be referred to as a manual system, theexternal programmer presents the collected intrinsic conduction data toa clinician who then programs the implantable device with parameterscomputed from the intrinsic conduction data by, for example, using aprinted lookup table and procedure. Unless otherwise specified,references to a system for computing or setting pacing parametersthroughout this document should be taken to include any of theautomated, semi-automated, or manual systems just described.

Some embodiments of the invention are directed to a process for pacing asynchronized chamber (left ventricle) using a pacing delay initiated byan intrinsic rate chamber (right ventricle) depolarization. Typically,the AV nodal conduction is gradual and does not change significantlywithin a beat. Based on this assumption, the technique used in thisembodiment can maintain the beat to beat Vp_(L) to Vs_(Rf) interval tobe substantially constant.

FIG. 4 is a timing diagram that illustrates pacing the synchronizedventricular chamber in accordance with embodiments of the invention. Thetiming diagram illustrates an initial cardiac cycle initiated by atrialevent A₀ followed by three cardiac pacing cycles, cycle 1, cycle 2,cycle 3 initiated by atrial events A₁, A₂, A₃. During cycle 1, the LVpace Vp₁ is delivered following a pacing escape interval RV₀-LV₁ that isinitiated by the right ventricular sense Vs₀ of the previous cycle.During cycle 2, the LV pace Vp₂ is delivered following a pacing escapeinterval RV₁-LV₂. During cycle 3, the LV pace Vp₃ is delivered followinga pacing escape interval RV₂-LV₃.

Initiating the pacing escape interval RV_(n-1)-LV_(n) from an intrinsicRV depolarization enhances fusion pacing of the LV during the followingbeat. The pacing delay RV_(n-1)-LV_(n) may change on a beat by beatbasis or within a certain number of beats that have a change in cyclelength. Initiation of the RV_(n-1)-LV_(n) pacing delay responsive to theintrinsic RV depolarization results in beat by beat alterations in thetiming of the LV pace. These beat by beat alterations in the LV pacetiming compensate for gradual changes in the timing of the RVdepolarizations so that the Vp_(n) to Vs_(n), intervals 451, 452, 453 ineach cycle remains relatively constant and fusion pacing is maintained.

FIG. 5 is a flow diagram illustrating a process of pacing using anoptimized pacing delay for an LV pace (RV_(n-1)-LV_(n)) that isinitiated by an intrinsic RV depolarization occurring in an immediatelypreceding cardiac cycle. During an initialization stage, the pacingdelay RV_(n-1)-LV_(n) may be initially optimized based on measuredintervals to achieve optimal coordination between intrinsic RVdepolarizations and LV paced depolarizations. In this embodiment, theRV_(n-1)-LV_(n) interval is initially optimized using measured atrialinterval (A-A) data and intrinsic RV atrioventricular interval (AVI_(R))data from one or more cardiac cycles. The A-A interval between a pacedor intrinsic atrial depolarization of a first cardiac cycle and thepaced or intrinsic atrial depolarization of the immediately subsequentcardiac cycle and the AVI_(R) are measured 510 for one or more cardiaccycles. An LV pacing escape interval is calculated 520 based on themeasured A-A interval and the measured AVI_(R). In one embodiment, theLV pacing escape interval, RV_(n-1)-LV_(n), may be calculated asfollows:RV _(n-1)-LV _(n)=(A-A)_(n-1)−(AVI _(Rn-1)-AVD _(Opt)),

where AVD_(Opt) may be calculated as previously described.

The pacing escape interval, RV_(n-1)-LV_(n), is started 530 relative tosensing an intrinsic RV depolarization of a first cardiac cycle. On thenext cardiac cycle, the LV is paced 540 relative to expiration of theRV_(n-1)-LV_(n) interval. AVI_(Rn-1)-AVD_(Opt) is a constant that isdetermined during initialization and can be periodically re-determined.The RV_(n-1)-LV_(n) interval may change on beat by beat basis due atleast in part to changes in the A-A interval.

FIG. 6A illustrates an embodiment of a therapy device 600 that may beused to deliver pacing therapy in accordance with embodiments of theinvention. The therapy device 600 includes a pulse generator 605electrically and physically coupled to an intracardiac lead system 610.Portions of the intracardiac lead system 610 are inserted into thepatient's heart.

The intracardiac lead system 610 includes one or more electrodesconfigured to sense electrical cardiac activity of the heart and deliverelectrical stimulation to the heart. Additionally, the cardiacelectrodes and/or other sensors may be used to sense the patient'stransthoracic impedance, and/or sense other physiological parameters,such as cardiac chamber pressure or temperature.

Portions of the housing 601 of the pulse generator 605 may optionallyserve as one or multiple can or indifferent electrodes. The housing 601is illustrated as incorporating a header 689 that may be configured tofacilitate removable attachment between one or more leads and thehousing 601.

The lead system 610 includes one or more cardiac pace/sense electrodes651-656 positioned in, on, or about one or more heart chambers forsensing electrical signals from the patient's heart and/or deliveringpacing pulses to the heart. The intracardiac sense/pace electrodes651-656, such as those illustrated in FIG. 6A, may be used to senseand/or pace one or more chambers of the heart, including the leftventricle, the right ventricle, the left atrium and/or the right atrium.The lead system 610 may include one or more defibrillation electrodes641, 642 for delivering defibrillation/cardioversion shocks to theheart.

The pulse generator 605 includes circuitry, such as filters, amplifiers,digitizers and/or other signal processing circuitry, used in conjunctionwith the cardiac electrodes 651-656 for sensing cardiac electricalsignals. Various signal features may be extracted and/or measured fromthe sensed cardiac signals, including R-waves, QRS features, and/or Q*deflections. Pacing controller circuitry disposed within the pulsegenerator 605 may incorporate circuitry capable of measuring variousintrinsic conduction intervals and other cardiac intervals such asintrinsic right and/or left atrioventricular intervals, A-A intervals,V-V intervals, QRS widths, interatrial and/or interventricularconduction delays.

In some embodiments, the pacing controller circuitry is configured tomeasure and use intrinsic conduction data to determine optimal pacingdelays such as AVD_(Opt), Q*-V_(p), and/or RV_(n-1)-LV_(n) as describedin more detail above. In some embodiments, the pulse generator 605transfers sensed or derived information relevant to the determination ofpacing delays to a patient-external device (not shown). Followingdownload of the implantably sensed or derived information, determinationof optimal pacing timing delays may be made by the patient-externaldevice or may be made by a human analyst. The pacing delays are thentransferred to the therapy device 600 and used to control the timing ofpacing pulses delivered to the heart.

Communications circuitry is disposed within the housing 601 forfacilitating communication between the pulse generator 605 and apatient-external device, such as an external programmer or advancedpatient management (APM) system, for example. The communicationscircuitry may also facilitate unidirectional or bidirectionalcommunication with one or more implanted, external, cutaneous, orsubcutaneous physiologic or non-physiologic sensors, patient-inputdevices and/or information systems.

The lead system 610 and pulse generator 605 may incorporate one or moresensors, such as a transthoracic impedance sensor and/or anaccelerometer which can be used to acquire information related to thepatient's hemodynamic need and/or movement. Information from thesesensors may be used to adapt the rate of pacing to the patient's levelof activity and/or hemodynamic requirements.

FIG. 6B illustrates an embodiment of a therapy device 600 that includesa pulse generator 605 and lead system as in FIG. 6A with the addition ofa His lead having a His electrode 650 arranged to sense His bundledepolarizations. The His lead may additionally incorporate a His ringelectrode 649 which provides for bipolar sensing of His bundleactivations. During implantation, the His bundle may be located throughtissue impedance measurements to facilitate placement of the Hiselectrodes 649, 650.

FIG. 7 is a block diagram depicting various components of a system thatmay be used to deliver pacing therapy in accordance with embodiments ofthe invention. The components, functionality, and configurationsdepicted are intended to provide an understanding of various featuresand combinations of features that may be incorporated in such a system.It is understood that a wide variety of device configurations arecontemplated, ranging from relatively sophisticated to relatively simpledesigns. As such, particular configurations may include some componentsillustrated in FIG. 7, while excluding other components. In certainembodiments, the arrangement of the functional blocks may vary from thearrangement depicted.

The system illustrated in FIG. 7 provides functionality for timingdelivery of pacing pulses based sensed early activation of a heartchamber. In some configurations, LV pacing delays may be timed fromintrinsic RV depolarizations of a prior cardiac cycle. In someembodiments, the functionality to measure intrinsic conduction and/oroptimize pacing delays is incorporated into an implantable device. Inother embodiments, the functionality may be incorporated in thepatient-external programmer. In yet other embodiments, the functionalitymay be divided between a patient implantable device and a patientexternal device.

The therapy system 700 illustrated in FIG. 7 includes a therapy controlprocessor 740 configured to control pacing therapy circuitry 730 togenerate pacing stimulations applied via the cardiac electrodes 725. Thetherapy control processor 740 may also control high energy shocksproduced by the defibrillation/cardioversion circuitry 735 for treatingtachyarrhythmia.

Cardiac signals are sensed using cardiac electrodes 725. The sensedcardiac signals are received by sensing circuitry 720, which includescircuitry and for amplifying, filtering and/or digitizing the cardiacsignals. The sensed cardiac signals may optionally be processed by noisereduction circuitry (not shown), which may reduce noise and or increasethe signal to noise ratio (SNR) of the signals before signals are sentto the control processor 740.

Circuitry 720 may be configured to detect various cardiac signalfeatures, such as R-waves, A-waves, QRS complexes, Q* deflections, Hisbundle activations, and/or other cardiac signal features. Circuitry 720may also be configured to measure intrinsic conduction intervals andother cardiac intervals, including intrinsic atrioventricular intervals(left and/or right), QRS widths, A-A intervals, V-V intervals and/orother cardiac intervals. Information from circuitry 720 is input to atherapy control processor 740. Using conduction information fromcircuitry 720, the optimization circuitry 775 calculates optimal pacingdelays. Pacing interval controller 765 times the optimal pacing delayswhich are initiated responsive to specific cardiac events, e.g., Q*and/or His bundle activation.

The therapy control processor 740 may include arrhythmia detectioncircuitry such as a signal processor that coordinates analysis of thesensed cardiac signals and/or other sensor inputs to detect cardiactachyarrhythmia. Rate based and/or morphological discriminationalgorithms may be implemented by the control processor 740 to detect andverify the presence and severity of an arrhythmic episode. If arrhythmiais detected, the therapy control processor 740 may coordinate deliveryof an appropriate therapy, such as anti-tachyarrhythmia pacing therapy(ATP), cardioversion, and/or defibrillation via thedefibrillation/cardioversion circuitry 735 to terminate or mitigate thearrhythmia.

Communications circuitry 750 is coupled to the control processor 740.The communications circuitry 750 allows communication between devices,such as patient-external devices 755 and patient-implantable devices. Inone configuration, the communications circuitry 750 and thepatient-external device 755 use a wire loop antenna and a radiofrequency telemetric link, as is known in the art, to receive andtransmit signals and data between the patient-external device 755 andcommunications circuitry 750. In this manner, programming commands anddata may be transferred to the control processor 740 from thepatient-external device 755 during and after implant. Using apatient-external programmer, a physician is able to set or modifyvarious parameters used by the therapy control processor 740. Forexample, a physician may set or modify parameters affecting monitoring,detection, pacing, and defibrillation functions of the therapy controlprocessor 740.

In certain embodiments, the control processor 740 transmits informationfor determination of pacing timing to the patient-external device 755.The information may include, for example, cardiac electrical signals,markers indicating the timing of certain features or points, measuredcharacteristics or features of the signals, and/or other information.The patient-external device 755 may use the transmitted information todetermine pacing timing intervals or may format and display informationto facilitate the determination of pacing delays by a human analyst.

Processes for timing the delivery of pacing pulses based on earlyactivation in accordance with embodiments of the invention may beimplemented by an implantable device, by a patient-external device, suchas a programmer or advanced patient management system, or by a manuallyimplementable procedure, such as by using a printed table lookup tocompute the optimal values, and/or by any combination of thesetechniques.

In one embodiment, the patient-external programmer 755 communicates withthe control processor 740 over a telemetry link and receives either rawelectrogram data, markers corresponding to particular sensed events,and/or measurements of intervals between sensed events or feature widthsas computed by the implantable device. The external programmer 755 maythen compute optimal settings for pacing timing intervals which areeither transmitted to the control processor 740 for immediatereprogramming or presented to a clinician operating the externalprogrammer as recommendations.

In another embodiment, the external programmer 755 may present the data,markers, and/or measurements to a human analyst who then programs thecontrol processor 740 in accordance with an algorithm. In yet a furtherembodiment, determination of the pacing timing may be fully automaticand performed by an implantable therapy device.

Various modifications and additions can be made to the preferredembodiments discussed hereinabove without departing from the scope ofthe present invention. Accordingly, the scope of the present inventionshould not be limited by the particular embodiments described above, butshould be defined only by the claims set forth below and equivalentsthereof.

What is claimed is:
 1. A method of operating a cardiac pacing device,comprising: measuring an atrial (A-A) interval and an intrinsicatrioventricular interval (AVI) of a first cardiac cycle; calculating apacing escape interval for a synchronized ventricular chamber based onthe measured A-A interval and the measured AVI; starting the pacingescape interval in response to sensing an intrinsic ventricular ratechamber depolarization of the first cardiac cycle; during a secondcardiac cycle immediately following the first cardiac cycle, pacing aventricular synchronized chamber relative to expiration of the pacingescape interval; and for each subsequent cardiac cycle, recalculatingthe pacing escape interval based at least on a measured A-A intervalfrom an immediately previous cardiac cycle.
 2. The method of claim 1,wherein the rate chamber is a right ventricle and the synchronizedchamber is a left ventricle.
 3. The method of claim 1, wherein the ratechamber is a left ventricle and the synchronized chamber is a rightventricle.
 4. The method of claim 1, wherein calculating the pacingescape interval is based on calculating a difference between theintrinsic atrioventricular interval of the first cardiac cycle and anoptimized synchronized chamber atrioventricular delay.
 5. The method ofclaim 1, wherein calculating the pacing escape interval comprisescalculating a difference between an intrinsic atrioventricular intervalof the first cardiac cycle and an optimized synchronized chamberatrioventricular delay subtracted from the A-A interval of the firstcardiac cycle.
 6. A method of operating a cardiac rhythm managementdevice, comprising: electrically coupling electrodes to multiplechambers of a heart; sensing cardiac electrical signals via theelectrodes and detecting cardiac signal features associated with cardiacevents; measuring one or more cardiac intervals, including intervalsbetween atrial events and atrioventricular intervals (AVIs) between anatrial event and a ventricular depolarization; calculating a pacingescape interval for a synchronized ventricular chamber based on ameasured A-A interval and a measured AVI for a first cardiac cycle;starting the pacing escape interval in response to sensing an intrinsicventricular rate chamber depolarization of the first cardiac cycle;pacing a ventricular synchronized chamber relative to expiration of thepacing escape interval during a second cardiac cycle immediatelyfollowing the first cardiac cycle; and recalculating the pacing escapeinterval for each subsequent cardiac cycle based at least on a measuredA-A interval of an immediately previous cardiac cycle.
 7. The method ofclaim 6, wherein pacing the ventricular synchronized chamber comprisesdelivering right and left ventricular paces substantiallysimultaneously.
 8. The method of claim 6, wherein pacing the ventricularsynchronized chamber comprises sequentially delivering right and leftventricular paces separated by an interventricular delay.